Papovaviruses are small DNA viruses that can induce tumor formation in certain mammalian hosts and transform primary mammalian cells of various organs to a fully neoplastic state. They do so at the hands of a small number of viral oncoproteins, each of which has proven itself capable of forming specific complexes with cellular proteins, the oncoprotein perturbation of which contributes to the evolution of a neoplastic phenotype. The existing repertoire of oncoprotein target polypeptides includes the products of both protooncogenes and tumor suppressing loci , some of which were first identified as contributors to the suppression or the promotion of neoplastic cell behavior through the molecular, genetic, and biological analysis of papovaviral oncoproteins. Indeed, many of the known protein targets participate in human cancer development. While the body of established papovaviral oncoprotein targets is substantial, it has become increasingly apparent from work in the field and in this Program that there are more such proteins yet to be discovered. With history as a precedent, from a full understanding of the nature of these target proteins and of their functions before and after oncoprotein binding, new insights into the mechanisms leading to tumor development in a mammalian host are likely to emerge. Thus, the primary goal of the next iteration of this program is to expand one's appreciation of how a group of recently discovered target proteins functions and how papovaviral oncoprotein binding perturbs them sufficiently to elicit a neoplastic effect. In addition, given the apparently incomplete nature of existing knowledge, we propose, as a group, to engage in an effort aimed at identifying all of the physically bound target polypeptides of each generic papovaviral oncoprotein species. The overarching goal of the work is to gain better insight into the molecular mechanisms that lead to human cancer development.